A number of mixtures of nucleic acid fragments are commercially available that can be used as markers for determining the sizes of nucleic acid molecules of experimental interest. For example, Collaborative Research, Inc. (Lexington, Mass.) has sold a marker ladder ("Quik-Kit Size Markers", cat. no. 30013) that is a mixture of 12 bacteriophage .lambda. (lambda) fragments. They are visualized by hybridization with two .sup.32 P-labeled 12-nucleotide synthetic oligonucleotides, complementary to the left and right bacteriophage cos sites.
A large number of other DNA marker fragments are available from numerous suppliers. In every case, except the Collaborative markers, these marker fragments are restriction digests of several bacteriophage or plasmid DNAS. Every DNA fragment in the digests can then be visualized by hybridization to the same bacteriophage or plasmid DNAS.
Other DNA marker ladders often use collections of fragments that have a quasi-random size distribution. For example, the quasi-random size distribution may be made by a digest of a DNA, often .lambda. DNA, by a single restriction enzyme. Alternatively, the fragments may vary linearly with molecular weight, i.e. adjacent bands may differ by about 1000 base pairs (e.g. "1 Kb DNA Ladder", cat. no. 5615SA, BRL, Gaithersburg, Md.). Bands in these linear ladders are not evenly spaced after electrophoresis, they are "compressed" in the "upper", higher molecular weight region of a gel. However some ladders have been constructed and sold that are logarithmically spaced ("GenePrint.TM.", cat. no. DG1911, Promega, Madison, Wis.).